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Effects of Variation in the Dietary Supply of Cysteine and Methionine on Liver Concentration of Glutathione and "Active Sulfate" (PAPS) and Serum Levels of Sulfate, Cystine, Methionine and Taurine: Relation to the Metabolism of Acetaminophen¹

Department of Pharmacology, State University of Groningen, Bloemsingel 1, 9713 BZ Groningen, The Netherlands

Amounts of the sulfur-containing amino acids methionine and cysteine in synthetic diets were decreased from 22.8 mmol methionine (=100 Met) and 26.4 mmol cysteine (=100 Cys) per kilogram diet in the control group to (Met/Cys) 100:0, 75:0, 50:0, 25:0 and 25:25, respectively, in experimental diet groups, in order to evaluate effects of limiting sulfur supply on the availability of cosubstrates for conjugation. Below a Met level of 22.8 mmol/kg growth rates decreased. Urinary excretion of inorganic sulfate decreased to 10–20% of control values in all groups. Feeding diets 100:0 and 75:0 for 14 days resulted in a decrease of the concentration of inorganic sulfate in serum; on diets 25:25 and 25:0 an increase was found. A decreased content of methionine/cysteine resulted in an increase in cystine, a decrease in taurine and no change in methionine concentration in serum. In all experimental groups the glutathione concentration in the liver diminished to about 20% of control values, and the hepatic concentration of "active sulfate" (PAPS: adenosine 3'-phosphate 5'-phosphosulfate) decreased in most rats. At the lowest methionine supply, sulfate conjugation of acetaminophen decreased to 50% of control. The formation of the acetaminophen glutathione conjugate remained unaffected, in spite of a decreased hepatic glutathione availability.

KEY WORDS: • cysteine • glutathione • sulfate • acetaminophen

¹ This work was financially supported by grant 13-28-66 from the Dutch Foundation for Medical Research FUNGO.

² Address of Dr. A. J. Baars: Department of Pharmacology, University of Leiden, Sylvius Laboratorium, Leiden, The Netherlands.

Manuscript received 20 December 1982.